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Impaired M‐Current and Neuronal Excitability
Author(s) -
Okada Motohiro,
Wada Kazumaru,
Kamata Akihisa,
Murakami Takuya,
Zhu Gang,
Kaneko Sunao
Publication year - 2002
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1046/j.1528-1157.43.s.9.9.x
Subject(s) - excitatory postsynaptic potential , bicuculline , dnqx , ampa receptor , medicine , endocrinology , neurotransmission , chemistry , inhibitory postsynaptic potential , neuroscience , pharmacology , biology , antagonist , glutamate receptor , receptor
Summary: Purpose: Benign familial neonatal convulsions (BFNC), a hereditary epilepsy, occurs specifically in newborns and remits spontaneously after this period. Several mutations of either KCNQ2 or KCNQ3, members of the KCNQ‐related K + ‐channel (KCNQ‐channel) family, were identified as a cause of BFNC. Such mutations impair KCNQ‐related M‐ current, an element of the inhibitory system in the central nervous system (CNS), and therefore are thought to result in neuronal hyperexcitability. Methods: To clarify the pathogenesis of BFNC, this study investigated the effects of the KCNQ channel on propagation of neuronal excitability using a 64‐channel multielectrode dish (MED64) system for novel two‐dimensional monitoring of evoked field potentials including fiber volley (FV) and field excitatory postsynaptic potential (fEPSP). Results: Dup996, a selective KCNQ‐channel inhibitor, did not affect the amplitude of FV or fEPSP, but enhanced the FV and fEPSP propagation. The γ‐aminobutyric acid (GABA) A ‐receptor antagonist, bicuculline, enhanced their propagation, whereas α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazolepropionate (AMPA)/glutamate‐receptor antagonist, DNQX, reduced both amplitude and propagation of fEPSP without affecting those of FV. Under the condition of GABA A ‐receptor blockade by bicuculline, Dup996 enhanced the amplitude of fEPSP and propagation of FV and fEPSP without affecting the amplitude of FV. Dup996 enhanced the stimulating effects of bicuculline on the propagation and amplitude of FV and fEPSP, but it did not affect the inhibiting effects of DNQX. Conclusions: These results suggest that the occurrence of BFNC cannot be produced by KCNQ‐channel dysfunction alone but by reciprocal action between impaired KCNQ channel and the other unknown.